SUMMARY Aging is a biological process that is the major risk factor for chronic disease and degeneration during the lifespan. However, it is beginning to be appreciated that disease and degeneration impinge on the aging process, in something perhaps akin to a feedback loop. This suggests that a better knowledge of one contributes to an understanding of the other. Furthermore, development of therapeutic interventions still must address the degenerative disorders of aging, while the search for broad interventions that target the biological aging process itself continues. The demographic and social developments associated with an aging population point to a real and deepening need for researchers who will provide the basic knowledge on aging that can be translated into solutions that are broadly applicable. Importantly, these researchers must more and more frequently be able to communicate effectively with practitioners in other disciplines and even to become part of multidisciplinary teams. The proposed Phase II COBRE in Aging and Regenerative Medicine will help fill this national need by mentoring junior investigators in the aging field within an interactive and multidisciplinary environment, while creating a dynamic center in which biomedical science targeting aging is practiced. The focus here is biomedical research with translation firmly in mind. However, this COBRE program is embedded within the multidisciplinary Tulane Center for Aging, and thus it can serve the purposes of addressing the broader challenges of an aging society. Notwithstanding these overarching goals, the individual research projects that are offered in this application have the promise of generating important new insights into a few focused areas of biological aging and regeneration. These projects build on our successes in COBRE Phase I, targeting central nervous system aging, immune system aging, degenerative disorders of the brain and musculoskeletal system, as well as the larger issues surrounding cell senescence and chronic inflammation.